Coccidioidomycosis Emergence in South America: Exploring Northeastern Brazil’s Epidemiological, Clinical, and Genomic Landscape

Coccidioidomycosis is an invasive mycosis included in WHO’s priority list. It is endemic and notifiable in the United States but neglected in Central and South America. We used a multi-institutional approach to assess whether disease characteristics, genetic variation in the pathogen or environmental factors affects the epidemiology of coccidioidomycosis and disease outcomes throughout the American continent. We identified 292 patients with coccidioidomycosis between 1978 and 2021 in the Piauí and Maranhão states of Brazil; the largest cases series reported outside the US/Mexico epidemic range. The male-to-female ratio was 57.4:1 and the main risk factor was armadillo hunting (91.1%) 4 to 30 days before symptom onset. Forty-two outbreaks involving two to six patients were observed. Most patients (92.8%) presented typical acute pulmonary disease, followed by disseminated (3.4%), chronic pulmonary (2.4%) and regressive pulmonary (1.4%). The most frequent clinical symptoms were cough (93%), fever (90%) and chest pain (77%). Mortality was observed in 8% of the patients. In 2004, and between 2015 and 2017, we observed a spike in coccidioidomycosis in Brazil, particularly in the state of Piauí. Unlike other main hotspots, the soil is acidic in this region and precipitation (p=0.015) and precipitation one-year prior (p=0.001) were predictors of higher coccidioidomycosis rates. The Brazilian strains are genotypically divergent from other described C. posadasii within the Texas/Mexico/South America clade. Coccidioidomycosis in Northeastern Brazil has a specific infection profile and armadillo hunters are at higher risk. Low pluviosity and extensive drought appear key to increasing the number of cases in Brazil. A unique C. posadasii lineage exists in Brazil; therefore, environmental, virulence, and/or pathogenesis traits may differ from other Coccidioides genotypes. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement National Council for Scientific and Technological Development (CNPq) grant number 434640/2018-2 ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Research Ethics Committee of the Institute of Tropical Diseases Nathan Portela, subsequently ratified by the Ethics Committee of the Federal University of Piauí (No.36/08 - CAAE 0036.0.045.000-8) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes